Introduction
Atrial septal defects (ASD) are one of the most common congenital heart defects with an estimated prevalence of 1.6 per 1000 live births [
1]. Most prevalent are ostium secundum defects followed by ostium primum and sinus venosus defects [
2]. Partial anomalous pulmonary venous connections (PAPVRs) are often associated with ASD, especially with sinus venosus defects. When repaired at a young age, patients with ASD have a life expectancy similar to the general population [
3,
4]. Left untreated, patients with large ASD gradually develop pulmonary hypertension, reversal of the left-to-right shunt and eventually right heart failure. In clinical practice, ASD closure is considered for patients with a shunt fraction greater than 1.5 [
2].
Multiple imaging modalities are used to detect and delineate these anatomic defects. Transthoracic echocardiography (TTE) is used as a primary screening modality. However, associated pathologies such as PAPVR are more difficult to identify with TTE. When TTE is inconclusive, transesophageal echocardiography (TEE) may be helpful [
5]. Alternatively, computed tomography (CT) and magnetic resonance imaging (MRI) are increasingly used.
MRI has shown its incremental value in congenital heart disease (CHD) [
6] and ASD in particular [
7]. MRI is the gold standard for noninvasive quantification of right heart function and shunt fraction [
8,
9]. It may detect intracardiac shunting and additional findings including PAPVR [
10]. However, it is performed with numerous breath-holds and relatively long examination times, which may be challenging for cardiac patients.
A promising and rapidly evolving MRI technique is 4D flow imaging, a volumetric, free-breathing acquisition technique of flow velocity data with simultaneous assessment of anatomic structures [
11]. The 4D flow MRI allows for flow quantification at any level within the acquired field of view and calculation of cardiac volumes and biventricular function [
12‐
14].
A few studies have evaluated the use of 4D flow MRI for visualization and quantification of cardiac shunts [
15‐
17]. It is not yet clear, however, whether this technique is robust across the range of imaging parameters that might be used in the clinical environment because of differences in body habitus or equipment. In the clinical setting, there may be heterogeneity in imaging techniques because of local preferences or needs for imaging parameters such as the signal-to-noise ratio (SNR), spatial resolution, scanning time, velocity-encoding speed (
Venc), available equipment, field strengths (1.5 T, 3 T) and patient body habitus. A previous paper showed that it is possible to measure venous flow even when using high
Venc [
18]. However, uncertainty remains about whether this technique is applicable outside of the research setting. As this technology has recently become more broadly clinically available, we seek to determine in this study whether 4D flow can robustly be used for the evaluation of cardiac shunts at different levels of the vascular tree using 4D flow data acquired across multiple centers—specifically measurements of the blood flow, shunt fraction and shunt volume.
Discussion
We show in this study that 4D flow MRI can be sufficient for evaluation of patients with ASD, including quantification of shunt fraction, and can be robustly performed at multiple institutions; 4D flow MRI is consistent and reliable for measuring systemic and pulmonic blood flow and obtaining shunt fractions at multiple levels across the vascular tree. In daily practice, a shunt fraction (
Qp/
Qs) threshold above 1.5 is often used as a critical parameter to determine the need for ASD closure. By 4D flow MRI, few patients had mixed results near the 1.5 threshold. In those patients, other clinical features may be used to decide upon individual surgical or medical management, such as right heart chamber enlargement or pulmonary pressure [
2,
5].
In this study, direct shunt volume quantification was obtained at the level of ASD by tracking the atrial septum frame by frame throughout the cardiac cycle. Direct shunt volume quantification was feasible in 69% of the patients and correlated well with calculated shunt volumes obtained by 4D flow measurements at the level of main arteries (Qp–Qs) (r = 0.955). Tracking the atrial septum may be challenging if there is insufficient image quality, if the size of the ASD is small or if there are multiple ASDs. For example, in two patients the direct quantification value was lower than the indirect quantification. When these cases were further reviewed, we found additional shunts, which were missed in the initial analysis (Supplementary Fig. 5). Therefore, we believe that direct quantification of each ASD can be helpful to determine whether all of shunts have been appropriately accounted for. Mismatch between direct and indirect measurements may point to additional undetected shunts.
We show in the current study that it is possible to achieve excellent multilevel and interreader reproducibility with 4D flow MRI at multiple centers. This alleviates some previous concerns that 4D flow might only be achievable at one or two centers with extensive experience. This is further supported by recent studies showing good scan-rescan reproducibility and good intraobserver agreement with 4D flow [
23,
24]. We further show here that experienced readers are not necessarily required to achieve high reproducibility. In addition, we demonstrate here that 4D flow can enable measurement of shunts at multiple alternative locations. This is especially helpful in the case of turbulent flow, aliasing or metallic artifacts. The 4D flow measurements can be performed at an alternative location distant to such artefacts to answer the clinical question. In patients with BAV, for example, flow acceleration across the aortic valve [
25] can compromise the accuracy of measurements in areas of turbulent flow [
26,
27], and an alternate measurement may be more accurate.
We present the current work, recognizing that 4D flow is an evolving imaging technique [
28,
29] and new strategies are being developed, including incorporation of multiple velocity encoding speeds [
30,
31]. To date, 4D flow has shown its potential for evaluation of congenital heart disease [
32], and is being introduced in daily clinical practice for other clinical indications [
33]. Additional work may be required to assess the performance of 4D flow in specific clinical scenarios. In the current work, we did not explore a direct comparison to other advanced imaging techniques, which can also be used to assess shunt fraction. For example, Yamasaki et al. propose CT as an approach for quantification of ASD [
34], obtaining ventricular stroke volumes from finely detailed anatomic data. However, without flow information provided by 4D flow or echocardiography, this approach may be confounded by concomitant valve regurgitation.
Limitations
We recognize a few potential limitations of the study. The patient population was not large, but we believe sufficient to demonstrate the robustness of the method. Second, although it is a study across multiple centers, all 4D flow acquisitions were performed using equipment from a single vendor. Additional work may be required to confirm similar quality 4D flow measurements can be obtained on other platforms. Third, a gadolinium-based contrast agent was used prior to image acquisition at all sites. Further work is needed to determine whether similar results can be obtained without intravenous contrast. In addition, we did not perform a direct comparison against 2D phase-contrast MRI in this study. We did find that flow measurements were consistent with stroke volumes obtained from anatomical data, which was reassuring. Multiple previous studies have compared 4D flow and 2D phase-contrast measurements, showing that measurements from each technique are generally consistent [
35,
36]. Bollache and colleagues showed better correlation between 4D flow and three-direction-velocity 2D phase-contrast than with the one-direction-velocity 2D phase-contrast technique, which is the most commonly used clinical technique [
36].
Conclusions
For patients referred for evaluation of ASD, 4D flow MRI showed excellent multilevel and interreader reproducibility for systemic and pulmonary blood flow measurements and shunt quantification obtained at different levels throughout the vascular tree.
Compliance with ethical standards
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